RNA regulons: coordination of post-transcriptional events

Key Points Transcription is surprisingly stochastic, yet protein production is precise, indicating the importance of post-transcriptional events in the regulation of gene expression. Transcription and translation are not directly coupled in eukaryotic cells, but intervening steps between them help to coordinate protein biosynthesis. RNA-binding proteins (RBPs) co-regulate functionally related mRNAs in ribonucleoprotein (RNP) modules at the steps of splicing, export, stability, localization and translation. Genome-wide methods identified subsets of functionally related mRNAs that associate with RBPs forming 'RNA operons', which drive the coordinated expression of these mRNAs. Some of these mRNAs undergo simultaneous decay, whereas some are translationally co-regulated by polysomes. Each mRNA can be co-regulated with others in multiple combinations; such structures of higher-order coordination can be defined as RNA regulons. RNA regulons dynamically exchange specific mRNAs during proliferation, differentiation, genotoxic treatments or biological cycles. Several RBPs are dysregulated and some mRNAs are defective in human diseases, indicating that mRNA regulons might be implicated in many pathological processes. RNA-binding proteins orchestrate the post-transcriptional co-regulation of subsets of mRNAs that encode functionally related proteins, thereby contributing to the coordination of gene expression in eukaryotes. Understanding the dynamics of such ribonucleoprotein structures might provide insights into some complex diseases and the regulation of gene expression during development. Recent findings demonstrate that multiple mRNAs are co-regulated by one or more sequence-specific RNA-binding proteins that orchestrate their splicing, export, stability, localization and translation. These and other observations have given rise to a model in which mRNAs that encode functionally related proteins are coordinately regulated during cell growth and differentiation as post-transcriptional RNA operons or regulons, through a ribonucleoprotein-driven mechanism. Here I describe several recently discovered examples of RNA operons in budding yeast, fruitfly and mammalian cells, and their potential importance in processes such as immune response, oxidative metabolism, stress response, circadian rhythms and disease. I close by considering the evolutionary wiring and rewiring of these combinatorial post-transcriptional gene-expression networks.